Fracture of model end-linked networks.

Advances in polymer chemistry over the last decade have enabled the synthesis of molecularly precise polymer networks that exhibit homogeneous structure. These precise polymer gels create the opportunity to establish true multiscale, molecular to macroscopic, relationships that define their elastic and failure properties. In this work, a theory of network fracture that accounts for loop defects is developed by drawing on recent advances in network elasticity. This loop-modified Lake-Thomas theory is tested against both molecular dynamics (MD) simulations and experimental fracture measurements on model gels, and good agreement between theory, which does not use an enhancement factor, and measurement is observed. Insight into the local and global contributions to energy dissipated during network failure and their relation to the bond dissociation energy is also provided. These findings enable a priori estimates of fracture energy in swollen gels where chain scission becomes an important failure mechanism.

Local dynamics and failure of inhomogeneous polymer networks.

Inhomogeneous crosslinked polymers are powerful platforms for materials design, because they can be synthesized from materials that provide complimentary properties to the resulting gel. For example, a membrane with both glassy and rubbery domains will be mechanically robust while enabling transport. The dynamics, and mechanical and failure properties of rubbery/glassy conetworks are only beginning to be studied, and there is likely to be strong heterogeneities in the dynamics and mechanical response. In this study, we use coarse-grained molecular dynamics simulations to generate microphase separated rubbery/glassy polymer networks with a bicontinuous morphology via in silico crosslinking. We study the effect of phase boundary on the local mobility gradient, and our simulation results reveal an asymmetric shift in the local mobility gradient across the interface that extends deeper into the phase with a lower Tg when the system temperature is between the glass transition temperatures of the two phases. Moreover, by employing a model that allows bond breaking, we examine the microscopic mechanism for failure in these networks as a function of the molecular weight of polymer strands between crosslinks and the number fraction of the glassy domain. Under uniaxial extension, we find that the stress is initially larger in the glassy domain. As the deformation proceeds, the segmental dynamics of the two phases homogenize, and subsequently bond breaking begins.

Natural Product Quercetin-3-methyl ether Promotes Colorectal Cancer Cell Apoptosis by Downregulating Intracellular Polyamine Signaling.

Dysregulation of cellular metabolism is a key marker of cancer, and it is suggested that metabolism should be considered as a targeted weakness of colorectal cancer. Increased polyamine metabolism is a common metabolic change in tumors. Thus, targeting polyamine metabolism for anticancer therapy, particularly polyamine blockade therapy, has gradually become a hot topic. Quercetin-3-methyl ether is a natural compound existed in various plants with diverse biological activities like antioxidant and antiaging. Here, we reported that Quercetin-3-methyl ether inhibits colorectal cancer cell viability, and promotes apoptosis in a dose-dependent and time-dependent manner. Intriguingly, the polyamine levels, including spermidine and spermine, in colorectal cancer cells were reduced upon treatment of Quercetin-3-methyl ether. This is likely resulted from the downregulation of SMOX, a key enzyme in polyamine metabolism that catalyzes the oxidation of spermine to spermidine. These findings suggest Quercetin-3-methyl ether decreases cellular polyamine level by suppressing SMOX expression, thereby inducing colorectal cancer cell apoptosis. Our results also reveal a correlation between the anti-tumor activity of Quercetin-3-methyl ether and the polyamine metabolism modulation, which may provide new insights into a better understanding of the pharmacological activity of Quercetin-3-methyl ether and how it reprograms cellular polyamine metabolism.

Development and internal validation of a prediction model to evaluate the risk of severe hemorrhage following mini-percutaneous nephrolithotomy.

PURPOSE: To develop a new prediction model for assessing the severe hemorrhage events in post mini-percutaneous nephrolithotomy (mini-PCNL) patients and internally validate it, thus to guide decision making in clinical practice. METHODS: The patients who underwent mini-PCNL were retrospectively reviewed. Potential risk factors were included as prediction variables for multivariate logistic regression analysis to identify independent risk factors, and prediction model was constructed. The predictive ability of the model was evaluated using the Concordance index (C-index) and Brier score. Bootstrapping resampling technique was used to perform internal validation. The related packages in R were used to generate the web application based on the prediction model. RESULTS: Multiple-tract was the strongest predictor of severe hemorrhage following mini-PCNL. Other risk factors were none or mild hydronephrosis, congenital anomalies of urinary system, urinary tract infection, operation time and stone peak Hounsfield unit. A prediction model was constructed to assess the probability of severe hemorrhage after mini-PCNL. The C-index and Brier score were 0.731 and 0.093, respectively after correcting for optimism, which signified the excellent discrimination and calibration. CONCLUSION: A new prediction model was developed to estimate risk of severe hemorrhage after mini-PCNL. It had been internally validated with good discrimination and calibration. The prediction model might be beneficial for endourologists in surgical decision-making and risk aversion.

Optically Controlled Femtosecond Polariton Switch at Room Temperature.

Exciton polaritons have shown great potential for applications such as low-threshold lasing, quantum simulation, and dissipation-free circuits. In this paper, we realize a room temperature ultrafast polaritonic switch where the Bose-Einstein condensate population can be depleted at the hundred femtosecond timescale with high extinction ratios. This is achieved by applying an ultrashort optical control pulse, inducing parametric scattering within the photon part of the polariton condensate via a four-wave mixing process. Using a femtosecond angle-resolved spectroscopic imaging technique, the erasure and revival of the polariton condensates can be visualized. The condensate depletion and revival are well modeled by an open-dissipative Gross-Pitaevskii equation including parametric scattering process. This pushes the speed frontier of all-optical controlled polaritonic switches at room temperature towards the THz regime.

Residue Behavior and Risk Assessment of Pyraclostrobin and Thifluzamide in Cowpea.

A rapid and sensitive analytical method for determination of pyraclostrobin and thifluzamide in cowpea was established based on QuEChERS sample preparation and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Average recoveries of pyraclostrobin and thifluzamide on cowpea were 100%-105% and 99%-105% with RSDs of 1%-5% and 2%-6%, respectively. The storage stability tests showed degradation rates of < 20% for samples stored at - 18℃ within 12 weeks. The field trials at eight locations in China showed that the residues of pyraclostrobin in cowpea at 3 and 5 days after spraying were 0.081-0.49 mg/kg and 0.029-0.48 mg/kg, and the residues of thifluzamide were 0.12-0.46 mg/kg and 0.047-0.50 mg/kg, respectively, which were all lower than the corresponding maximum residue limits in China. The dissipation of both pyraclostrobin and thifluzamide in cowpea were fast with half-lives (T1/2) of 1.5-2.3 days and 1.7-2.4 days. This study provided risk assessment data for establishment of good agricultural practice in cowpea plant.

Lactobacillus paracasei R3 protects against dextran sulfate sodium (DSS)-induced colitis in mice via regulating Th17/Treg cell balance.

Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis (UC) and Crohn's Disease, are most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. Strategies that target the microbiota have emerged as potential therapies and, of these, probiotics have gained the greatest attention. Herein, we isolated a strain of Lactobacillus paracasei R3 (L.p R3) with strong biofilm formation ability from infant feces. Interestingly, we also found L.p R3 strain can ameliorate the general symptoms of murine colitis, alleviate inflammatory cell infiltration and inhibit Th17 while promote Treg function in murine dextran sulfate sodium (DSS)-induced colitis. Overall, this study suggested that L.p R3 strain significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.

Ectodysplasin A receptor (EDAR) promotes colorectal cancer cell proliferation via regulation of the Wnt/ß-catenin signaling pathway.

Colorectal cancer is the second leading cause of cancer mortality worldwide with poor prognosis and high recurrence. Aberrant Wnt/ß-catenin signaling promotes oncogenesis by transcriptional activation of c-Myc and its downstream signals. EDAR is characterized as an important effector of canonical Wnt signaling in developing skin appendages, but the interplay between EDAR and Wnt signaling in tumorigenesis and progression remains to be elucidated. In this study, we revealed that EDAR expression is prevalently elevated in colorectal cancer tissues compared with normal tissues. Further analysis suggests there is a strict correlation between EDAR expression and colorectal cancer progression. EDAR silencing by shRNA in colorectal cancer cells showed proliferative suppression via retarding cell cycle at G1 phase. Xenograft mice transplanted with shEDAR-transduced tumor cells significantly alleviated tumor burden in comparison with control mice. Furthermore, downregulation of EDAR was accompanied by reduction of ß-catenin, c-Myc and other G1 cell cycle regulators, while ß-catenin agonist restored the expression of these proteins and overrode the proliferative block induced by EDAR knockdown. These findings indicate that EDAR functions as a component of Wnt/ß-catenin signaling pathway, and is a potential modulator in colorectal carcinogenesis.

Upregulation of miR-196b-5p attenuates BCG uptake via targeting SOCS3 and activating STAT3 in macrophages from patients with long-term cigarette smoking-related active pulmonary tuberculosis.

BACKGROUND: Cigarette smoking (CS) triggers an intense and harmful inflammatory response in lungs mediated by alveolar and blood macrophages, monocytes, and neutrophils and is closely associated with prevalence of tuberculosis (TB). The risk of death in patients with long-term cigarette smoking-related pulmonary tuberculosis (LCS-PTB) is approximately 4.5 times higher than those with nonsmoking pulmonary tuberculosis (N-PTB). However, the mechanisms underlying the harmful inflammatory responses in the setting of LCS-PTB have not been well documented. METHODS: 28 cases LCS-PTB patients, 22 cases N-PTB patients and 20 cases healthy volunteers were enrolled in this study. Monocytes were isolated from peripheral blood mononuclear cells. Differentiated human MDM and U937 cell were prepared with M-CSF and PMA stimulation, respectively. The miR-196b-5p, STAT1, STAT3, STAT4, STAT5A, STAT5B, STAT6, SOCS1 and SOCS3 mRNA expression were detected by qRT-PCR. Western blot was performed according to SOCS1, SOCS3, and pSTAT3 expression. The mycobacterial uptake by MDMs from different groups of patients after Bacillus Calmette-Guérin (BCG) infection and agomir-196b-5p or antagomir-196b-5p transfection were used by flow cytometry analysis. Human IL-6, IL-10 and TNF-α levels on the plasma and cell culture supernatant samples were measured using ELISA. For dual-luciferase reporter assay, the SOCS3 3'-UTR segments, containing the binding elements of miR-196b-5p or its mutant versions were synthesized as sense and antisense linkers. RESULTS: In this study, we found that IL-6, TNF-α production, SOCS3 mRNA expression were downregulated, while miR-196b-5p and STAT3 mRNA expression were upregulated in monocytes from LCS-PTB patients as compared to N-PTB patients. Meanwhile, we demonstrated that miR-196b-5p could target SOCS3 and activate STAT3 signaling pathway, which may possibly contribute to attenuation of BCG uptake and decrease in IL-6 and TNF-α production in macrophages. CONCLUSIONS: Our findings revealed that CS exposure regulates inflammatory responses in monocyte/macrophages from LCS-PTB patients via upregulating miR-196b-5p, and further understanding of the specific role of miR-196b-5p in inflammatory responses mightfacilitate elucidating the pathogenesis of LCS-PTB, thus leading to the development of new therapeutic strategies for PTB patients with long-term cigarette smoking.

Dynamically consistent method for mixed quantum-classical simulations: A semiclassical approach.

We introduce a new semiclassical (SC) framework, the Mixed Quantum-Classical Initial Value Representation (MQC-IVR), that can be tuned to reproduce existing quantum-limit and classical-limit SC approximations to quantum real-time correlation functions. Applying a modified Filinov transformation to a quantum-limit SC formulation leads to the association of a Filinov parameter with each degree of freedom in the system; varying this parameter from zero to infinity controls the extent of quantization of the corresponding mode. The resulting MQC-IVR expression provides a consistent dynamic framework for mixed quantum-classical simulations and we demonstrate its numerical accuracy in the calculation of real-time correlation functions for a model 1D system and a model 2D system over the full range of quantum- to classical-limit behaviors.

Treating adolescent pseudomyopia and elevated intraocular pressure using chiropractic and moxibustion: A CARE-compliant case report.

RATIONALE: This case report aims to provide clinical evidence on the effectiveness of integrating chiropractic and moxibustion techniques for treating pseudomyopia accompanied by elevated intraocular pressure resulting from cervical spine issues because the application of complementary medicine modalities for managing such vision disorders currently lacks adequate investigations. PATIENT CONCERNS: A 6-year-old patient presented with blurred vision, intermittent ocular discomfort, and upper cervical discomfort. DIAGNOSES: Spine-related increased intraocular pressure and pseudomyopia. INTERVENTIONS: The patient received integrative treatment of chiropractic and walnut-shell moxibustion 3 times a week for a total of 10 treatment sessions. OUTCOMES: The patient exhibited progressive improvements in visual acuity and reductions in intraocular pressure over the treatment period, with unaided vision exceeding 2 lines of improvement in visual acuity charts and normalized intraocular pressure after 10 treatment sessions. These therapeutic effects were sustained at 3-month follow-up. LESSONS: The integrative use of chiropractic and walnut-shell moxibustion demonstrates considerable potential in alleviating symptoms of pseudomyopia, reducing intraocular pressure, and restoring visual function in spine-related pseudomyopia cases.

Efficacy and safety of transcutaneous auricular vagus nerve stimulation (ta-VNS) in the treatment of tinnitus: protocol for an updated systematic review and meta-analysis.

INTRODUCTION: With an increasing incidence and significant effects on patients, tinnitus has become a major disease burden. There is a dearth of therapies with established efficacy for tinnitus. Transcutaneous auricular vagus nerve stimulation (ta-VNS) is being investigated as a potential therapy for tinnitus, but the current body of evidence remains inconclusive due to conflicting results across different studies. As a result, this protocol aims to synthesise and update the evidence to clarify whether ta-VNS is effective and safe for alleviating tinnitus. METHODS AND ANALYSIS: To identify relevant randomised controlled trials (RCTs), seven representative bibliographical databases will be searched from their inception to December 2023: PubMed, Embase (via OVID), Cochrane Library, Chinese National Knowledge Infrastructure, Wangfang Database, Chinese BioMedical Literature Database, and Chongqing VIP Chinese Science and Technology Periodical Database. Publications in English or Chinese will be considered for inclusion. RCTs comparing ta-VNS with active treatments, no intervention, waitlist control or sham ta-VNS in adult patients with subjective tinnitus will be included. Studies on objective tinnitus will be excluded. Primary outcome is tinnitus symptom severity measured by validated scales. With all eligible trials included, when applicable, quantitative analysis via meta-analyses will be performed using RevMan V.5.4.1 software. Otherwise, a qualitative analysis will be conducted. The methodological quality of the included RCTs will be assessed using the Risk of Bias 2.0 tool. Sensitivity analyses, subgroup analysis and publication bias evaluation will also be performed. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to grade the certainty of the evidence. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review, as no primary data will be collected. The results will be reported and disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022351917.

Professor FU Wenbin's experience of "acupuncture-moxibustion-consolidation" holistic idea in treatment of laryngeal herpes zoster with vocal cord paralysis. / 符文彬教授整合思维"一针二灸三巩固"模式治疗喉带状疱疹伴声带麻痹的临床经验.

This paper introduces professor FU Wenbin's clinical experience in the treatment of laryngeal herpes zoster with vocal cord paralysis, using the holistic mode of treatment, in which, acupuncture, moxibustion and consolidation regimens are integrated. Regarding the core pathogenesis of the disease, the invaded exogenous toxic heat is transformed into fire that flows to the throat. Soothing liver and releasing heat is the general principle of treatment, guiding the entire process of treatment. For acupuncture regimen, the filiform needling is used and the acupoint prescription is composed of Baihui (GV 20), Yintang (GV 24+), Lianquan (CV 23), the four-gate points (bilateral Hegu [LI 4] and Taichong [LR 3]), the group points for conducting qi back to the primary (Zhongwan [CV 12], Xiawan [CV 10], Qihai [CV 6] and Guanyuan [CV 4]), as well as bilateral Fengchi (GB 20), Wangu (GB 12) and Yifeng (TE 17). Besides, the pricking technique is delivered to the posterior wall of the pharynx for soothing the liver, regulating the spirit, reducing the heat and benefiting the throat. For the moxibustion regimen, moxibustion is applied to Fengchi (GB 20), Feishu (BL 13), the four-flower points (bilateral Geshu [BL 17] and Danshu [BL 19]), Shenshu (BL 23) and Mingmen (GV 4), which nourishes the spleen and stomach and reduces the heat pathogen through the heating action of moxibustion specially. In the stage of consolidation, the bloodletting and cupping technique is used at Xinshu (BL 15), Ganshu (BL 18) and Jianjing (GB 21) to eliminate the liver stagnation and the intradermal needling is delivered to sustain the needling stimulation and consolidate the therapeutic effect.

The efficacy of electroacupuncture for cervical nerve edema and movement disorder caused by the brachial plexus injury: a case report.

The brachial plexus injury (BPI) is one of the most severe types of peripheral nerve injuries, often caused by upper limb traction injury. In clinic, the surgery is widely used to treat the BPI. However, surgery may need to be performed multiple times at different stages, which carries risks and brings heavy economic burden. In non-surgical treatment, splinting, local injection of corticosteroids, and oral corticosteroids can achieve significant short-term benefits, but they are prone to recurrence and may cause complications of mechanical or chemical nerve damage. In this report, we present a case of a 46-year-old female patient with BPI. The patient had difficulty in raising, flexing and extending of the left upper limb, and accompanied with the soreness and pain of neck and shoulder. After 3 months of EA treatment, a significant reduction in the inner diameter of the left C5 to C7 root at the outlet of brachial plexus nerve was detected by musculoskeletal ultrasound, and the soreness and pain in the left neck and shoulder were significantly reduced. The soreness and pain in the left neck and shoulder did not recur for 2 years. Case summary: The patient is a 46-year-old female with BPI. She experienced difficult in lifting, flexing and extending of the left upper limb, which accompanied by soreness and pain in the left neck and shoulder. After 3 months of EA treatment, the patient's pain and limb's movement disorder was improved. After 2 years of follow-up, the patient's left neck and shoulder showed no further pain. Conclusion: EA has shown satisfied efficacy in BPI, improving limb restrictions and relieving pain in patients for at least 2 years.

Application of functional near-infrared spectroscopy (fNIRS) in tinnitus research: contemporary insights and perspectives.

Tinnitus, characterized by phantom sound perception, is a highly disruptive condition lacking clearly effective treatments. Its complex neural mechanisms are not fully elucidated. Functional near-infrared spectroscopy (fNIRS) is a promising neuroimaging tool well-suited for assessing tinnitus due to its quietness, portability, and ability to directly measure cortical hemodynamic responses. This study timely summarizes the recent applications of fNIRS in investigating tinnitus pathology, correlating neuroimaging biomarkers with symptom severity, and evaluating treatment efficacy. Further studies with larger samples are warranted to reproduce existing findings. Thus, fNIRS appears to be a promising tool in tinnitus research. Addressing technical limitations, optimizing control groups, advancing data analysis, integrating standardized, and individualized experimental protocols can facilitate the extended and robust utilization of fNIRS in tinnitus research.

Towards provably efficient quantum algorithms for large-scale machine-learning models.

Large machine learning models are revolutionary technologies of artificial intelligence whose bottlenecks include huge computational expenses, power, and time used both in the pre-training and fine-tuning process. In this work, we show that fault-tolerant quantum computing could possibly provide provably efficient resolutions for generic (stochastic) gradient descent algorithms, scaling as [Formula: see text], where n is the size of the models and T is the number of iterations in the training, as long as the models are both sufficiently dissipative and sparse, with small learning rates. Based on earlier efficient quantum algorithms for dissipative differential equations, we find and prove that similar algorithms work for (stochastic) gradient descent, the primary algorithm for machine learning. In practice, we benchmark instances of large machine learning models from 7 million to 103 million parameters. We find that, in the context of sparse training, a quantum enhancement is possible at the early stage of learning after model pruning, motivating a sparse parameter download and re-upload scheme. Our work shows solidly that fault-tolerant quantum algorithms could potentially contribute to most state-of-the-art, large-scale machine-learning problems.

Ultrafast dynamics of exciton-polariton fluids at non-zero momenta.

In this study, we have explored the ultrafast formation and decay dynamics of exciton-polariton fluids at non-zero momenta, non-resonantly excited by a small-spot femtosecond pump pulse in a ZnO microcavity. Using the femtosecond angle-resolved spectroscopic imaging technique, multidimensional dynamics in both the energy and momentum degrees of freedom have been obtained. Two distinct regions with different decay rate in the energy dimension and various decay-channels in the momentum dimension can be well-resolved. Theoretical simulations based on the generalized Gross-Pitaevskii equation can reach a qualitative agreement with the experimental observations, demonstrating the significance of the initial potential barrier induced by the pump pulse during the decay process. The finding of our study can provide additional insights into the fundamental understanding of exciton-polariton condensates, enabling further advancements for controlling the fluids and practical applications.

Perceived stress and brain connectivity in subthreshold depression: Insights from eyes-closed and eyes-open states.

Perceived stress is an acknowledged risk factor for subthreshold depression (StD), and fluctuations in perceived stress are thought to disrupt the harmony of brain networks essential for emotional and cognitive functioning. This study aimed to elucidate the relationship between eye-open (EO) and eye-closed (EC) states, perceived stress, and StD. We recruited 27 individuals with StD and 33 healthy controls, collecting resting state fMRI data under both EC and EO conditions. We combined intrinsic connectivity and seed-based functional connectivity analyses to construct the functional network and explore differences between EC and EO conditions. Graph theory analysis revealed weakened connectivity strength in the right superior frontal gyrus (SFG) and right median cingulate and paracingulate gyrus (MCC) among participants with StD, suggesting an important role for these regions in the stress-related emotions dysregulation. Notably, altered SFG connectivity was observed to significantly relate to perceived stress levels in StD, and the SFG connection emerges as a neural mediator potentially influencing the relationship between perceived stress and StD. These findings highlight the role of SFG and MCC in perceived stress and suggest that understanding EC and EO states in relation to these regions is important in the neurobiological framework of StD. This may offer valuable perspectives for early prevention and intervention strategies in mental health disorders.

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.